Although liver transplant for decompensated cirrhosis secondary to Wilson disease is well accepted, the use of transplant for patients with severe neurologic manifestations of this condition remains controversial, and these can be perceived as a contraindication. Here, we describe a 45-year-old woman who presented with an incidental hepatocellular carcinoma at the time of transplant. The patient had severe neurologic manifestations of Wilson disease pretransplant, including dysarthria, hyperreflexia, asymmetrical ataxia, tremor, bradyphrenia, and shuffling gait...

BACKGROUND: The high prevalence and severity of methamphetamine (MA) abuse demands greater neurobiological understanding of its etiology. METHODS: We conducted immunoblotting and in vivo microdialysis procedures in MA high/low drinking mice, as well as in isogenic C57BL/6J mice that varied in their MA preference/taking, to examine the glutamate underpinnings of MA abuse vulnerability. Neuropharmacological and Homer2 knockdown approaches were also used in C57BL/6J mice to confirm the role for nucleus accumbens (NAC) glutamate/Homer2 expression in MA preference/aversion...

Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence...

High rates of relapse after prolonged abstinence are often triggered by exposure to drug-associated cues that induce drug craving. Incubation of drug craving is a phenomenon that consists of time-dependent increases in cue-induced drug craving during withdrawal. Plasticity mechanisms in the nucleus accumbens (NAc) underlie drug-seeking responses and involve changes in excitatory synaptic transmission's efficacy. In particular, the prefrontal cortex (PFC) glutamatergic input to the NAc core has been well characterized regarding cocaine-evoked plasticity following non-contingent versus contingent exposure to cocaine or alternatively after protracted abstinence...

Negative reinforcement is widely thought to play an important role in chronic alcohol-use disorders (AUDs), and high comorbidity between AUDs and affective disorders highlights the importance of investigating this relationship. Prominent models posit that repeated cycles of alcohol (ethanol, EtOH) exposure and withdrawal produce circuit adaptations in the central nervous system that drive a transition from positive- to negative reinforcement-based alcohol seeking. Evidence supporting this theory has accumulated in large part using forced EtOH administration models, such as chronic intragastric gavage and chronic vapor inhalation...

BACKGROUND: Reward and energy homeostasis are both regulated by a network of hypothalamic neuropeptide systems. The melanin-concentrating hormone (MCH) and its MCH-1 receptor (MCH1-R) modulate alcohol intake, but it remains unknown to what extent this reflects actions on energy balance or reward. Here, we evaluated the MCH1-R in regulation of caloric intake and motivation to consume alcohol in states of escalated consumption. METHODS: Rats had intermittent access (IA) to alcohol and were divided into high- and low-drinking groups...

Since the work of Johnson and North, it is known that opiates increase the activity of dopaminergic neurons by a GABA neuron-mediated desinhibition. This model should however be updated based on recent advances. Thus, the neuroanatomical location of the GABA neurons responsible for this desinhibition has been recently detailed: they belong to a brain structure in continuity with the posterior part of the ventral tegmental area and discovered this past decade. Other data also highlighted the critical role played by glutamatergic transmission in the opioid regulation of dopaminergic neuron activity...

A 39-year-old homeless man was found confused and incoherent after ingesting an estimated total of 200 tablets of various medications. He presented to the emergency department with delirium, tachycardia, clonus and hyperthermia of 38.0°C. His condition worsened rapidly with his temperature rising to 39.9°C despite active cooling. The patient was subsequently sedated, intubated, paralysed and admitted to the intensive care unit, where he remained for 38 days. His initial presentation of a large mixed drug overdose manifested as serotonin syndrome, which had a protracted course complicated by ethanol withdrawal...

Osmotic Demyelination Syndrome includes Central Pontine Myelinolysis and Extrapontine Myelinolysis. This condition has been described in cases of chronic Alcohol Dependence Syndrome and in rapid correction of hyponatremia. Though we frequently see patients with Alcohol Dependence Syndrome presenting with complicated withdrawal, Central Pontine Myelinolysis remains largely undetected and under-reported in literature. We present here a case of protracted Delirium Tremens where MRI brain revealed Central Pontine Myelinolysis...

Current pharmacological treatments for alcohol dependence have focused on reducing alcohol consumption, but to date there are few treatments that also address the negative affective symptoms during acute and protracted alcohol withdrawal which are often exacerbated in people with comorbid anxiety and depression. Selective serotonin reuptake inhibitors (SSRIs) are sometimes prescribed to ameliorate these symptoms but can exacerbate anxiety and cravings in a select group of patients. In this critical review, we discuss recent literature describing an association between alcohol dependence, the SERT linked polymorphic region (5-HTTLPR), and pharmacological response to SSRIs...

Unified theories of addiction are challenged by differing drug-seeking behaviors and neurobiological adaptations across drug classes, particularly for narcotics and psychostimulants. We previously showed that protracted abstinence to opiates leads to despair behavior and social withdrawal in mice, and we identified a transcriptional signature in the extended amygdala that was also present in animals abstinent from nicotine, Δ9-tetrahydrocannabinol (THC) and alcohol. Here we examined whether protracted abstinence to these four drugs would also share common behavioral features, and eventually differ from abstinence to the prototypic psychostimulant cocaine...

BACKGROUND: In Canada and other developed countries, the majority of neonatal deaths occur in tertiary neonatal intensive care units. Most deaths occur following the withdrawal of life-sustaining treatments. AIM: To explore neonatal death events and end-of-life care practices in two tertiary neonatal intensive care settings. DESIGN: A structured, retrospective, cohort study. SETTING/PARTICIPANTS: All infants who died under tertiary neonatal intensive care from January 2009 to December 2013 in a regional Canadian neonatal program...

BACKGROUND: Increased levels of cortisol during acute alcohol withdrawal have been linked to cognitive deficits and depression. Preclinical research found that the glucocorticoid Type II receptor antagonist, mifepristone, prevented some of the neurotoxic effects of withdrawal and memory loss. Clinical trials have shown mifepristone effective in the treatment of depression. This study aims to examine the extent to which the glucocorticoid Type II receptor antagonist, mifepristone, when given to alcohol dependent males during the acute phase of alcohol withdrawal, will protect against the subsequent memory loss and depressive symptoms during abstinence from alcohol...

Aocoholism in the elderly determines tne protracted nature or tne pathological craving for etnanol in post-abstinence syndrome period, restricts arsenal of active pharmacotherapy and updates the search for new pharmacological therapeutic strategies. The results showed that the inclusion of the drug "Remaxol" in the treatment of clinical manifestations of craving for ethanol in post-abstinence syndrome period of associated forms of alcoholism in the elderly provides better in relation to conventional therapy dynamics of reduction of somatovegetative and neurological manifestations of alcohol withdrawal syndrome, as well as the main components of craving for alcohol, will increase the efficiency of outpatient treatment at the stage of remission...

High rates of relapse to drug use during abstinence is a defining feature of drug addiction. In abstinent drug users, drug relapse is often precipitated by acute exposure to the self-administered drug, drug-associated cues, stress, as well as by short-term and protracted withdrawal symptoms. In this review, we discuss different animal models that have been used to study behavioral and neuropharmacological mechanisms of these relapse-related phenomena. In the first part, we discuss relapse models in which abstinence is achieved through extinction training, including the established reinstatement model, as well as the reacquisition and resurgence models...

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of heroin dependence. BDNF expression is dramatically changed during drug withdrawal, and is associated with drug withdrawal syndrome. This study aimed to explore (1) alterations of BDNF serum levels in heroin-dependent patients after long term abstinence; and (2) the association between BDNF serum levels and protracted withdrawal syndrome. METHOD: Fifty-three male heroin-dependent patients and fifty-two gender-matched healthy controls were enrolled in this study...

In individuals with a history of drug taking, the capacity of drug-associated cues to elicit indices of drug craving intensifies or incubates with the passage of time during drug abstinence. This incubation of cocaine craving, as well as difficulties with learning to suppress drug-seeking behavior during protracted withdrawal, are associated with a time-dependent deregulation of ventromedial prefrontal cortex (vmPFC) function. As the molecular bases for cocaine-related vmPFC deregulation remain elusive, the present study assayed the consequences of extended access to intravenous cocaine (6 hours/day; 0...

Although alcoholism and depression are highly comorbid, treatment options that take this into account are lacking, and mouse models of alcohol (ethanol (EtOH)) intake-induced depressive-like behavior have not been well established. Recent studies utilizing contingent EtOH administration through prolonged two-bottle choice access have demonstrated depression-like behavior following EtOH abstinence in singly housed female C57BL/6J mice. In the present study, we found that depression-like behavior in the forced swim test (FST) is revealed only after a protracted (2 weeks), but not acute (24 h), abstinence period...

Effects of withdrawal from ethanol drinking in chronic intermittent ethanol vapor (CIE)-exposed dependent rats and air-exposed nondependent rats on proliferation and survival of progenitor cells in the hippocampus and the medial prefrontal cortex (mPFC) were investigated. Rats were injected with 5'-Bromo 2-deoxyuridine 72 h post-CIE to measure proliferation (2 h-old cells) and survival (29-day-old cells) of progenitors born during a time-point previously reported to elicit a proliferative burst in the hippocampus...

AIM: Occasional babies survive long term after withdrawal of intensive care despite a poor prognosis. We aimed to review in detail the clinical cases, characteristics, and outcomes of neonates with unexpected protracted survival following planned withdrawal of intensive cardiorespiratory support. METHODS: We reviewed infants who unexpectedly survived for more than one week following planned withdrawal of intensive care in two tertiary-level NICUs over a seven-year period...